1st Subgroup Research Articles

Real-world outcomes of pyrotinib-based therapy for HER2-positive breast cancer with brain metastases: A multicentre, retrospective analysis

ObjectiveThis study was designed to investigate the efficacy and safety of pyrotinib-based therapy for HER2-positive breast cancer with brain metastases (BM) in the real-world setting. MethodsData of HER2-positive breast cancer patients with BM treated with pyrotinib-based therapy from a multicetre, registered, real-world study were analyzed. ResultsAmong 45 female patients, the overall objective response rate (ORR) was 62.2%, higher in 1st/2nd-line than ≥3rd-line (71.0% vs. 42.9%, P=0.072). The objective response rate of intracranial lesions (CNS-ORR) was 71.1 %, with a significantly higher CNS-ORR observed in the 1st or 2nd-line subgroup compared to that of ≥3rd-line subgroup (83.9% vs. 42.9%, P<0.05). By the end of follow-up, 20 patients (44.4%) died, and the 1-year survival rate was 73.3%. The median progression-free survival (PFS) was 9.1 months (95% CI 6.7-11.5). Patients with 1 or 2 BM had a longer median PFS of 12.0 months compared to 7.7 months for those with ≥3 BM (P=0.01). In addition, 1- or 2-line therapy and full dose exposure of pyrotinib of 320mg-400mg/day were associated with improved median PFS (all P>0.05). The median intracranial PFS (CNS-PFS) was 11.4 months (95% CI 7.5-15.3). However, local intervention plus systemic treatment seemed to prolong CNS-PFS compared with systemic treatment alone (13.7 vs. 9.1 months, P=0.128). Diarrhea was most common (88.9%), 24.4% grade 3. ConclusionsThe pyrotinib-based therapy is effective for HER-2 positive breast cancer with BM, especially in 1st- or 2nd-line treatment, with tolerable adverse events. However, insufficient dosing of pyrotinib may impair efficacy outcomes.Micro Abstract: This study is aimed to investigate the efficacy and safety of pyrotinib-based chemotherapy against human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases (BM) in the real-world setting. The clinical outcome data of HER2-positive breast cancer patients with BM treated with pyrotinib-based therapy from a multicenter, registered, real-world study were comprehensively analyzed. Our study showed that the pyrotinib-based therapy could be effective for HER-2-positive breast cancer with BM, especially in first- or second-line treatments, with tolerable adverse events.

LEVELS OF HEAT SHOCK PROTEIN HSP70 IN NEURONS OF PARIETAL CORTEX AND HIPPOCAMPUS IN RATS WITH VARIOUS STAGES OF CEREBRAL ISCHEMIA

The paper examines the issue of increasing the body’s resistance to oxygen deficiency and energy deficit under cerebral ischemia. Adaptation to these changes is represented by an increased number of heat shock proteins in brain neurons. Their expression increases with a decrease of oxygen level in the blood. The aim of the paper is to evaluate HSP70 level in the brain of rats with various stages of cerebral ischemia. Materials and Methods. The study was conducted on 27 white outbred male rats weighing 267±16 g. The authors used such models as partial cerebral ischemia, step-by-step 90 % blood flow shutdown, one-time 90 % blood flow shutdown, and complete cerebral ischemia. Results. In the 1st subgroup of step-by-step 90 % blood flow shutdown (7 days between dressings) there was an increase in the HSP70 level by 25 % in the parietal cortex (p&lt;0.05) compared with the control. However, its concentration in the hippocampus did not change (p&gt;0.05). In the 2nd and 3rd subgroups of step-by-step 90 % blood flow shutdown (3 days and 1 day between dressings), the HSP70 level did not change in any of the studied areas (p&gt;0.05) compared with the control. Compared with the 1st subgroup, in the 2nd subgroup HSP70 level in the parietal cortex was lower by 26 % (p&lt;0.05) and in the hippocampus by 20 % (p&lt;0.05), in the 3rd subgroup it was lower by 30 % (p&lt;0.05) and by 23 % (p&lt;0.05), respectively. No differences in HSP70 levels were found between the 2nd and 3rd subgroups (p&gt;0.05). In the group of one-time 90 % blood flow shutdown, the HSP70 level decreased by 29 % in the parietal cortex (p&lt;0.05) and by 18 % in the hippocampus (p&lt;0.05) compared with the control. In group of one-time 90 % blood flow shutdown, the HSP70 level did not differ from those in the 2nd and 3rd subgroups of step-by-step 90 % blood flow shutdown in the hippocampus. In the parietal cortex, the HSP70 level in the 2nd subgroup was 28 % higher (p&lt;0.05), and in the 3rd subgroup by 23 % higher (p&lt;0.05) compared with the group of one-time 90 % blood flow shutdown. In total cerebral ischemia, the most significant decrease in HSP70 level was observed compared to the control: by 35 % in the parietal cortex (p&lt;0.05) and by 36 % in the hippocampus (p&lt;0.05). Conclusion. Thus, in the 1st subgroup with the maximum interval between dressings, the HSP70 level increased, indicating the activation of compensation mechanisms during hypoxia by protecting proteins from premature proteolytic breakdown and promoting the correct polypeptide folding into a tertiary structure.

Clinical and non-hemorrhagic neuroimaging indicators of probable cerebral amyloid angiopathy as a cause of non-traumatic lobar hematomas

Objective. To identify clinical and non-hemorrhagic neuroimaging indicators of probable CAA in patients with acute non-traumatic lobar hematomas. Cerebral amyloid angiopathy (CAA) is a microangiopathy affecting the leptomeningial and cortical vessels of the brain due to the deposition of pathological b-amyloid in them. The most common clinical manifestation of CAA is lobar hematomas (LH) – spontaneous intracerebral hemorrhages localized between the cerebral cortex and basal ganglia. LH can also occur in hypertensive cerebral microangiopathy (hCMA) in patients with arterial hypertension. Since the tactics of managing patients with CAA and hCMA differ, it is important to determine the genesis of LH correctly. Materials and methods. A comparative analysis of clinical and neuroimaging characteristics of acute non-traumatic hypertension in 32 patients with probable CAA and hCMA was carried out. Along with neurological examination and neuroimaging, all patients underwent a study using the Montreal Cognitive Assessment Scale and the Benson Complex Figure Test to reveal visuospatial impairments. The diagnosis of probable CAA was carried out in accordance with the updated Boston criteria of 2010, the diagnosis of hCMA was based on clinical data, anamnesis and results of neuroimaging of the brain. Results. Probable CAA was diagnosed in 16 patients, and in all these cases it was combined with hCMA (1st subgroup). Isolated hCMA as a cause of LH was also observed in 16 patients (2nd subgroup). Patients of subgroup 1 were statistically significantly more likely to have clinically pronounced visual impairments, performed the MoCA subtest and the Benson Complex Figure Test worse, and the overall assessment of their cognitive functions according to Mo SA was lower than in patients of subgroup 2. According to neuroimaging data, in the 1st subgroup of patients, an expansion of perivascular spaces in the semi-oval center and a zero or negative value of the front-occipital gradient were more often detected. The application of the logistic regression method made it possible to integrate potential CAA indicators and create a prognostic model for revealing this pathology in patients with hypertension. Conclusions. Clinically pronounced disorders of primary and higher visual functions, a negative front-occipital gradient and expansion of perivascular spaces in the semi-oval centers can serve as indicators of probable CAA in patients with acute lobar hematoma. On admission of such patients to the vascular center, it is advisable to include iron-sensitive pulse sequences in the neuroimaging screening protocol to verify the diagnosis of CAA.

Latent sensitization as a mask of the problem of frequently ill preschool children in Rostov-on-Don

Objective: to identify the frequency and etiology of latent sensitization among frequently ill preschool children living in Rostov-on-Don.Materials and methods: 40 preschool-age children (5.3±1.2 years old) who are under medical supervision for frequent respiratory diseases of a protracted nature were examined. According to the nature of the clinical course, the following subgroups were identified: 1st subgroup — frequently ill children with recurrent respiratory tract pathology: adenoiditis, bronchoobstructive syndrome (n=19), 2nd subgroup — frequently ill children with different duration of episodes of acute respiratory diseases: from 3 to 5 days and from 5 to 10 days. The mandatory criterion for inclusion in the group was the absence of hereditary burden due to allergic pathology. All patients underwent an allergological examination, including the determination with the help of an automatic immunochemiluminescent analyzer (Immuno CAP 100 Phadia AB, Switzerland) of specific blood IgE to the antigens of Timothy's meadow, rPh1 p1, Phl p 5; antigens of Altenaria alternata, rAlt a1; antigens of ragweed, nAmb a1; to the antigens of wormwood nArt v1.Results: sensitization to the main allergens that are causally significant for the region is formed in 33–74% of cases in frequently ill preschool children living in Rostov-on-Don. The main causally significant allergen, sensitization to which is diagnosed in most of the subjects, is the major fraction of Ragweed Ragweed (nAmb a1). Sensitization to the major fraction of the common Wormwood allergen (nArt v1) is not diagnosed in a monovariant, but always accompanies hypersensitivity to high Ragweed ragweed.Conclusions: the presence of concomitant pathology of the respiratory tract in the form of adenoiditis, bronchoobstructive syndrome, as well as a long (more than 5 days) course of frequently recurrent acute respiratory diseases is a factor indicating a high probability of latent sensitization in frequently ill preschool children, which is formed in 33-74% of cases. It is recommended that frequently ill children with symptoms of recurrent respiratory tract pathology perform allergodiagnostics with the identification of specific IgE to the main causally significant allergens for the region.

Assessment of the Need for Surgical Debridement of Periapical Tissues Among Patients of Older Age Groups as a Manifestation of Ageism

Endodontic therapy is aimed at cleaning the root canal system and creating barriers to prevent re-infection of roots and peripical tissues. The presence of persistent bacteria or reinfection of a previously mechanically treated and disinfected root system causes the development of apical periodontitis and the need to implement surgical aids. Against the background of an increase in the number of patients of older age groups, characterized by obliteration of the root canal system, the relevance of surgical aids for apical periodontitis increases. At the same time, based on their own life experience, patients of older age groups may perceive the refusal to perform orthodontic therapy and the offer of surgical benefits as age-related egoism. Purpose of work: to study the severity of periapical changes and indications for surgical intervention among patients of older age groups. Materials and methods. The endodontic and periapical status of 300 patients was assessed in the 1st subgroup aged 60 to 70 years and the 2nd subgroup aged over 71 years. The results of the study. The greatest number of ageist conclusions in assessing the feasibility of providing surgical benefits was revealed in women with higher education.

Abstract CT207: Association of gene expression profiles and clinical outcomes in patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma treated with pembrolizumab in KEYNOTE-629

Abstract Background: Pembrolizumab (pembro) monotherapy demonstrated clinically meaningful antitumor activity for both locally advanced (LA) and recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC) in the phase 2 KEYNOTE-629 trial (NCT03284424). cSCC has high immunogenicity driven by a high tumor mutational burden and it is of interest to determine if the 18-gene T-cell inflamed gene expression profile (TcellinfGEP) and a set of other signatures relevant to the tumor microenvironment are associated with response to treatment. This retrospective analysis aimed to evaluate the association between GEP signatures and clinical outcomes in patients (pts) treated with pembro in KEYNOTE-629. Methods: Pts with histologically confirmed LA or R/M cSCC, measurable disease per RECIST v1.1, ECOG PS 0 or 1 received pembro 200 mg IV Q3W ≤35 cycles. Association between TcellinfGEP by RNAseq with clinical response (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]) to pembro, and association between a set of additional consensus signatures with clinical response to pembro adjusted for TcellinfGEP were evaluated. Significance of GEP signatures was prespecified at 0.05 for 1-sided P values from logistic (ORR) and Cox proportional hazard regression (PFS, OS) adjusted for ECOG PS. Additional assessments included TcellinfGEP AUC or Harrell’s C-index in predicting response to pembro. Results: Of 159 pts, 143 (n = 52, LA cSCC; n = 91, R/M cSCC) had RNAseq samples available for analysis. Of 143 pts, 33.6 % had a TcellinfGEP &amp;lt;1st tertile and 66.4% had a TcellinfGEP ≥1st tertile. TcellinfGEP was significantly associated with improved ORR (P = 0.040) but not PFS (P = 0.087) or OS (P = 0.709). None of the 10 other consensus signatures were significantly associated with clinical outcomes after adjusting for TcellinfGEP and multiplicity (P &amp;gt; 0.05). AUC of TcellinfGEP was moderately predictive of ORR (0.61, 95% CI, 0.51-0.70). Harrell’s C-index of TcellinfGEP was moderately predictive of PFS (0.57, 95% CI 0.51-0.63), and duration of response (0.56, 95% CI 0.38-0.73), but not predictive of OS (0.50, 95% CI 0.42-0.57). Median PFS (95% CI) was 4.1 mo (1.4-9.8) for the TcellinfGEP &amp;lt;1st tertile subgroup and 8.5 mo (5.5-21.0) for TcellinfGEP ≥1st tertile subgroup. Median OS (95% CI) for the TcellinfGEP &amp;lt;1st tertile subgroup was 25.1 mo (11.4-NR) and 21.0 mo (15.8-29.8) for the TcellinfGEP ≥1st tertile subgroup. Conclusions: In this retrospective analysis of KEYNOTE-629, Tcellinf GEP was associated with tumor objective response to pembro, but was not clearly associated with longer survival in pts with LA or R/M cSCC treated with pembro. While definitive conclusions require more analyses, these findings provide additional support for TcellinfGEP as a predictive biomarker for cSCC. Citation Format: Åse Bratland, Jean-Jacques Grob, Eva Munoz Couselo, Laurent Mortier, Ralf Gutzmer, Osama Roshdy, Rene Mendoza Gonzalez, Jacob Schachter, Ana M. Arance Fernandez, Florent Grange, Nicolas Meyer, Abhishek J. Joshi, Salem Billan, Judong Shen, Razvan Cristescu, Michael Nebozhyn, Andrey Loboda, Jason Sparkowski, Burak Gumuscu, Jianda Yuan, Brett Hughes. Association of gene expression profiles and clinical outcomes in patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma treated with pembrolizumab in KEYNOTE-629 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT207.

Частота рецидивов ретинопатии недоношенных после введения ингибиторов ангиогенеза (афлиберцепта) в зависимости от массы тела ребенка

Purpose. To study the effectiveness of treatment and the causes of reactivation of retinopathy (ROP) in premature children after aflibercept injection. Material and methods. This study was conducted at the V.F. Voino-Yasenetsky Scientific and Practical Center for Specialized Medical Care in Children from September 2021 to February 2023. The study included 122 premature infants (244 eyes) with ROP who received intravitreal administration of aflibercept. Patients were divided into two groups: the main group (reactivation group) consisted of children who received two or more intravitreal injections of VEGF inhibitors (aflibercept) and the control group consisted of children who received a single intravitreal injection of VEGF inhibitor (aflibercept) with a positive effect. In addition, 3 subgroups were identified depending on birth weight: 37 children had a birth weight of less than 900 g (1st subgroup), 41 children weighed from 900 to 1200 g (2nd subgroup), and 44 children weighed more than 1200 g (3rd subgroup). All patients were monitored for reactivation of ROP after intravitreal injection of aflibercept. Results. Since 2010, we have been using angiogenesis inhibitors in the treatment of ROP. The effectiveness of one dose of aflibercept (0,5 mg/0,0125 ml) is 84,84%. Repeated injections are easily tolerated by patients and increase the effectiveness of treatment to 99,76%. The work is devoted to the analysis of reactivation of ROP after one injection of aflibercept and the study of the reasons for repeated injections. 37/244 eyes (15,16%) showed reactivation of ROP after one injection. Factors influencing the reactivation of retinopathy of prematurity after intravitreal injection of aflibercept include: gestational age, postconceptual age at the 1st injection, birth weight, weight at the 1st injection, birth height, newborn head circumference, head circumference at the 1st injection, newborn chest circumference, history of blood transfusions, body mass index (BMI) at the 1st injection, nuchal cord complications. A large dependence of the reactivation rate on the child’s weight was noted. The birth weight subgroup of less than 900 g had a recurrence rate of 28,38%, followed by the average birth weight subgroup (12,20%) and the subgroup weighing more than 1200 g (6,82%). The reactivation time in the three subgroups of patients was 9,82±5,76, 10,20±3,27 and 12,33±9,24 weeks, respectively. The time of reactivation was also determined by the child’s weight. Reactivation occurred earlier in children with lower weight: in three subgroups of patients, 9.82±5.76, 10.20±3.27 and 12.33±9.24 weeks, respectively. Conclusion. Based on our research, the frequency of reactivation of ROP depends on the weight of the premature baby. A change in weight, even by 100 grams, changes the course of ROP. The lower the birth weight is, the higher the reactivation rate of ROP becomes. Reactivation of ROP occurs 4 times more often (in every 3–4 children) in children with very low birth weight (less than 900 g). The frequency of reactivation is also determined by the weight of the child during the first injection of an angiogenesis inhibitor. Weight also determines the time of reactivation, occurring in children weighing less than 900 or 9–10 weeks after the first injection. If there are risk factors, it is advisable to: carry out simultaneous injections in both eyes, which will increase the dose of aflibercept in total, carefully monitor them in the first 2 months with examination of the fundus, or increase the dose of the drug. Effectiveness can be enhanced by ingesting synergists or impact of physiotherapy. Key words: recurrence, reactivation, retinopathy of prematurity, risk factor, birth weight, intravitreal injection, aflibercept, vascular endothelial growth factor

Biochemical predictors of preclinical arteriosclerosis in patients with chronic obstructive pulmonary disease after COVID-19

This article presents the findings of an open, comparative, prospective study aimed to investigate the state of vascular endothelial function in patients with chronic obstructive pulmonary disease (COPD) who have recovered from COVID-19, and to assess the potential for long-term prediction of preclinical atherosclerosis development.Materials and methods. A total of 133 COPD patients were examined under outpatient conditions: the main group (n=90), with a history of COVID-19, and a comparison group (n=43). Participants were examined twice: V1 - initial examination from 3 weeks to three months post-infection, V2 - a follow-up examination 12 months after the first visit. Based on the CAVI index values at point V2, the main group was divided into 2 subgroups. The state of vascular endothelial function was assessed using volume sphygmomanometry and by determining the concentration of biochemical markers in the blood.Results. In the main group at point V2, the studied parameters of arterial stiffness were significantly higher compared to the comparison group (aortic pulse wave velocity, cardio-ankle vascular index (CAVI) on the right and left, augmentation indices on the brachial and carotid arteries). At point V1, in the 1st subgroup (R-CAVI≥8.5 units), the concentration of biomarkers such as endothelin-1, total homocysteine, monocyte chemoattractant protein, vascular endothelial growth factor, C-reactive protein, interleukin-6,10 was significantly higher than in the 2nd subgroup (R-CAVI&lt;8.5 units). Conclusion. Taking into account the results obtained, a mathematical model for predicting preclinical atherosclerosis in COPD patients 12 months after COVID-19 was developed, which can be applied by clinicians in the long-term assessment of cardiovascular risk. Key words: chronic obstructive pulmonary disease, COVID-19, sphygmomanometry, predictors, prognosis, CAVI index&gt; ˂ 8.5 units).Conclusion. Taking into account the results obtained, a mathematical model for predicting preclinical atherosclerosis in COPD patients 12 months after COVID-19 was developed, which can be applied by clinicians in the long-term assessment of cardiovascular risk.

PROFILE OF NITRIC OXIDE METABOLISM INDICATORS IN PRETERM INFANTS WITH PERINATAL CENTRAL NERVOUS SYSTEM INJURIES

Introduction. Premature infants often experience a heightened risk of brain damage, potentially leading to various disorders affecting motor, cognitive, behavioral, social, and sensory functions. The underlying pathological processes of hypoxic-ischemic central nervous system (CNS) injury predominantly stem from compromised cerebral blood flow and oxygen transport. Timely diagnosis and treatment options for prematurely born children with perinatal CNS damage remain limited. Nitric oxide, a universal regulator of physiological functions, plays a crucial role. Endothelial dysfunction, marked by the loss of the neurovascular protective functions of nitric oxide, could significantly contribute to the development of cognitive impairment in hypoxic-ischemic CNS damage. Objectives. The study aims to evaluate the specificities of nitrate metabolism indicators in premature infants with hypoxic-ischemic CNS lesions in the early neonatal period. This involves examining and comparing clinical indicators characterizing hemodynamics, as well as the levels of nitrites, nitrates, and nitrosothiols in urine among patients in the studied groups. Subjects and Methods. The study comprised 14 premature infants with hypoxic-ischemic CNS injury (main group), with a separate selection of 4 infants who did not survive during the neonatal period. The comparison group included 20 relatively healthy prematurely born children. Stratification was based on the results of a genetic study, specifically the determination of the rs61722009 polymorphism of the eNOS gene. The patients underwent routine clinical examinations, including blood pressure measurements, and assessments of nitrates, nitrites, and nitrosothiols in urine. Subgroups were identified as follows: 1st subgroup - 4bb (n=10), and 2nd subgroup - 4aa/4ab (n=10). Results. It was observed that newborns who did not survive had significantly lower systolic and diastolic blood pressure readings on the first day of life, in comparison to relatively healthy children in the two control subgroups (day 1 - p=0.018; p=0.027; p=0.036; p=0.053). Additionally, they exhibited lower heart rate indicators on the first day (p=0.001; p=0.002). However, overall, hemodynamic indicators in newborns with hypoxic-ischemic central nervous system damage did not show statistically significant differences from the corresponding indicators in relatively healthy children. The results indicate a significantly lower level of diuresis in children who died as a result of severe with hypoxic-ischemic central nervous system damage, probably due to the development of multiple organ failure immediately after birth. As a result, it was found that the levels of nitrites (p&lt;0.001; p&lt;0.0001) and nitrates (p&lt;0.01; p&lt;0.0001) were reduced in children with with hypoxic-ischemic central nervous system damage, compared to children in the control groups, regardless of genotype variant. While the level of nitrosothiols did not differ significantly, it was even much higher in children who did not survive, 3.55±0.39 vs 2.23±0.22; p=0.008. The differences found may indicate a disruption of the regulatory effect of nitric oxyde on vascular tone and the condition of neuroglia, particularly in children with hypoxic-ischemic central nervous system damage, as a result of its insufficient production, as well as insufficient mobilization from the depot due to nitrite and nitrate reductases. Conclusions. Hemodynamic patterns in children from the examined groups, except for those who did not survive, did not exhibit significant differences. The notably lower urine output in deceased children indicates the development of multiple organ failure due to severe hypoxia. In children with hypoxic-ischemic central nervous system damage, there is a reduction in the levels of nitrites and nitrates in urine compared to relatively healthy premature infants, while the level of nitrosothiols did not show significant differences and was even notably higher in children who did not survive. The outcome of studying the levels of nitrates, nitrites, and nitrosothiols in urine in a larger patient sample may lead to the development of an algorithm for early diagnosis and management, contingent on the severity of metabolic disorders resulting from hypoxia, considering the potential influence of nitric oxide on energy deficit and mitochondrial dysfunction.

POTENTIAL FOR PATHOGENETIC CORRECTION OF PROTEASE-ANTIPROTEASE SYSTEM IMBALANCE IN PATIENTS WITH COMORBIDITY OF STABLE ANGINA PECTORIS OF THE II-III FUNCTIONAL CLASS AND STAGE II-III CHRONIC OBSTRUCTIVE PULMONARY DISEASE

The aim of this study is to assess the clinical effectiveness of the therapy including exogenous L-arginine and statins under the comorbidity of stable angina pectoris of the II-III functional class and chronic obstructive pulmonary disease of the II-III stage.&#x0D; Materials and methods. The study included 50 patients with coronary heart disease and chronic obstructive pulmonary disease (mean age 57 years; male/female ratio 78/22%). In order to assess the clinical effectiveness of the therapy for combined cardiopulmonary pathology, the patients were randomized into 2 subgroups: subgroup 1 included 25 patients who took metabolitotropic medication under high-intensity statin therapy (the basic therapy included L-arginine and rosuvastatin as a hypolipidemic agent in a dose of 20 mg/day); subgroup 2 included 25 patients who received only basic therapy under moderately intensive statin therapy (daily doses of atorvastatin 20 mg, rosuvastatin 10 mg)). The groups were comparable in terms of gender distribution and demographic characteristics. Comparative analysis of smoking experience, initial smoking age and smoking history did not differ significantly between the groups. After 12±1 weeks, a control examination was carried out.&#x0D; Results. The analysis of the ratio of the MMP-9 activity level before and after the therapy showed that the level of MMP-9 expression decreased by 43.28% (p&lt;0.05) in the 1st subgroup and by 13.18% in the 2nd subgroup until the end of the therapy. TIMP activity after 12 weeks of the treatment was +33.11% (p&lt;0.05) and +11.27% for the 1st and 2nd subgroups respectively. The difference between subgroups 1 and 2 in the level of the CRP marker before and after the therapy was -45.65% (p&lt;0.05) and -9.09%, respectively. 76% of people from the 1st subgroup reached the target level of healthy people before the completion of the therapy that is significantly higher than the similar indicator in the 2nd subgroup (32%) at χ2=8.05, p&lt;0.01.&#x0D; Conclusions: The application of L-arginine alongside high-intensity statin therapy for patients presenting with stable angina pectoris of the II-III functional class and stage II-III chronic obstructive pulmonary disease (COPD) resulted in more notable positive changes in the modulation of protease-antiprotease status disorders. This was evidenced by a reduction in the heightened expression of MMP-9 and an increase in the level of TIMP during the course of treatment.

Metabolic activity of bone tissue osteoblasts in patients with chronic pancreatitis

Objective — to investigate the level and role of osteocalcin in patients with chronic pancreatitis, to determine the dependence of changes in this indicator on the vitamin D receptor gene. Materials and methods. Examinations involved 70 patients with chronic pancreatitis (CP), who formed the main group. Women (46 or 66.4%) prevailed in this group. The age of the patients was from 29 to 43 years, the mean age 33.2±2.1 years. Control group consisted of 78 practically healthy subjects. The groups were comparable in terms of age and gender ratio. The diagnostic search included the study of the polymorphism of vitamin D receptor (VDR) gene and the biochemical marker of bone tissue, osteocalcin. Their possible effects on the course of the disease and the formation of complications have been investigated. Results. In the process of determining the VDR gene polymorphism, the significant difference was found in the distribution of gene alleles (χ2=30.08, df=4; p &lt;0.01). According to the results of genetic testing, both groups of patients were divided into three subgroups: 1st subgroup (bb‑genotype carriers), 2nd subgroup (Bb‑genotype carriers), 3rd subgroup (BB‑genotype carriers). In the control group, the distribution was as follows: 27 (38.6%), 34 (48.6%) and 9 (12.8%) patients, in the main group — 13 (18.5%), 30 (42.8%) and 27 (38.7%) patients. With the presence of CP, there was a change in the distribution of alleles towards the BB genotype of the VDR gene, which was associated with a higher risk of osteoporosis. 35 (50.0%) patients with CP and 3 (3.8%) individuals from the control group had a history of bone fractures (p &lt;0.01). In CP, the average osteocalcin level was 22.20±2.53 ng/ml, 27 (38.6%) patients had normal levels, 15 (55.6%) of them had the Bb genotype, 7 (25.9%) — genotype BB, in 5 (18.5%) — genotype bb. A decrease in the level of osteocalcin below the norm (to 12.7±1.87 ng/ml) was registered in 4 (5.7%) patients, of which 2 (50.0%) had the BB genotype, 1 (25.0%) — Bb genotype, another 1 (25.0%) — bb genotype. A higher than normal level of osteocalcin (45.1±23.24 ng/ml) was recorded in 39 (55.7%) patients of the main group, of which 18 (43.6%) had the BB genotype, 14 (35.9%) — Bb genotype, 7 (20.5%) — bb genotype. Conclusions. The course of CP in most cases is accompanied by an increase in osteocalcin levels, which can be considered as an indicator of a violation of the mineral density of bone tissue. Changes in the ratio of genotypes of the VDR gene are registered in patients with CP, which gives reason to assume a violation of the absorption of vitamin D due to genetic aberrations. In the majority of patients with CP, in the presence of an unfavorable genotype (BB) of the VDR gene, an increase in the content of osteocalcin is observed, which can be explained by one of the ways of the formation of osteoporotic conditions — a violation of the differentiation of osteoblasts. Chronic pancreatitis can be considered as an unfavorable nosology that provokes interference in bone metabolism with a high probability of formation of osteoporotic conditions, which requires early diagnosis and prevention of complications.

The role of single immunoglobulin interleukin-1–related receptor in formation of necrotising enterocolitis in infants with intrauterine infection

Necrotizing Enterocolitis is one of the actual problems that primarily affects premature infants, particularly those born before 32 weeks of gestation. The aim of this study is to investigate the role of genetic factors in the development of both necrotizing enterocolitis and intrauterine infection, exploring the possible links between these two conditions. A total of 52 with NEC and 10 healthy, were included in this study. All the examined children with NEC were divided into 2 groups: 19 newborns with intrauterine infection (1st subgroup), 33 infants without intrauterine infection (2nd subgroup). It was determined SIGIRR gene mutations with DNA isolation and standardized PCR reactions. It was found that C58 gene locus changes is a potential predictive marker for differentiating between infants with intrauterine infection and NEC and those without these conditions. Genetic screening may help identify infants at higher risk of developing NEC, allowing for targeted interventions and personalized care.

Clinical signs of the quality level of fixed dentures in the process of use and rationale for feasibility of their replacement

The growing requirements for the quality of dental care necessitates expert evaluation of dental prostheses. Therefore, on the way to improve the structure and process of providing dental care, it is important to analyze the primary data of its results in quantitative and qualitative terms. The purpose of this work is to clarify the content and results of consulting care by analyzing clinically important indicators of the quality of fixed dentures that determine their applicability for further use. Among the 410 patients aged 35-81 examined for damage to abutment teeth and periodontal tissues, unsatisfactory condition of crowns and bridges, the 1st subgroup included 76 (18.5%) persons who sought counseling on their own initiative and the 2nd subgroup – 334 (81.5%) persons with referrals from other medical institutions. Quality indicators of 759 artificial crowns and 803 bridges were determined (K08.5 – unsatisfactory restoration of teeth) in the early (up to 24 months) and remote (more than 24 months of use) periods of observation using a modified index of clinical and technological quality. In patients of both groups in the early observation period 67 crowns and 101 bridges (all signs – 253), and in the remote period – 692 crowns and 702 bridges (3804 signs) of low quality were revealed. Quality index of these structures in the early and remote periods of observation was 0,71 versus 0,36 (p&lt;0.05) and 0.64 versus 0.37 respectively (p&lt;0.05). In 71 (93.4%) patients of the 1st group grounds for replacement of 292 out of 327 (89.3%), and in 238 (71.3%) patients of the 2nd group – 827 (67.0%) out of 1235 fixed partial dentures were found. Thus, expert assessment of the quality of dental care is an integral part of ensuring the predicted results of prosthetic treatment. The proposed method of assessing the clinical and technological quality of fixed dentures makes it possible to determine their suitability or unsuitability for further use.

Features of hormonal homeostasis in women with functional hypothalamic amenorrhea and premature ovarian insufficiengy caused by posttraumatic stress disorder.

Posttraumatic stress disorder can cause severe and prolonged amenorrhea in women. Since the beginning of the war in Ukraine, there has been an increased number of visits for the medical care of female military servicewomen and displaced women with this problem.The objective: to perform a comprehensive study of the characteristics of the hormonal levels of the hypothalamic-pituitary-ovarian axis and the stress hormone cortisol, as well as to analyze the presence of autoantibodies to ovarian tissue in women with secondary amenorrhea caused by posttraumatic stress disorder.Materials and methods. The levels of hypothalamic-pituitary-ovarian hormones (follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol, progesterone, free testosterone and anti-Mullerian hormone (AMH), as well as cortisol (urine), autoantibodies to ovarian tissue from 54 military servicewomen and displaced women with amenorrhea caused by posttraumatic stress disorder (main group). 35 (64.8%) women (the 1st subgroup) were diagnosed with functional hypothalamic amenorrhea (FHA), 19 (35.2%) patients (the 2nd subgroup) were diagnosed with premature ovarian failure (POF).The control group included 23 women of reproductive age (18–37 years), who were in a state of psychological comfort and had no menstrual cycle disorders.Results. As a result of the study, a significant (p&lt;0.05) decrease of all pituitary-ovarian hormones was found in women with FHA, except for free testosterone and AMH. In patients with POF, there was an increased concentration of pituitary hormones and a decreased amount of estradiol by 2.2 times, progesterone by 3.9 times, and AMH by 21.0 times compared to the control group.A 1.5-fold increase in prolactin level in patients with POF compared to the indicator of the control group is noteworthy. The presence of autoantibodies in the group with POF was detected in 26.3% of cases (in the group of women with FHA – only in 2.9% of cases; p&lt;0.05), which may be a manifestation of polyglandular autoimmune syndrome.In both examined subgroups of the main group, a probable increased cortisol concentration in daily urine was determined (by 2.0 times in the 1st subgroup and by 2.1 times in the 2nd subgroup compared to the control), which indicates a stressogenic dysfunction of the adrenal glands.Conclusions. Posttraumatic stress disorder can have an irreversible pathological effect on the reproductive system of women. In women with stressogenic functional hypothalamic amenorrhea there is a deep depression of the hypothalamic-pituitary-ovarian axis with preserving the follicular ovarian apparatus.In women with premature ovarian failure (POF) with long-term stress, there is a sharp depletion of the ovarian reserve. The presence of autoantibodies to ovarian tissue indicates the involvement of the immune system in the pathogenetic chain of development of amenorrhea, the severity of the lesion and the higher speed of the follicle atresia process by POF.

Исследование предоперационной симметрии дистанции «экватор хрусталика – цилиарные отростки» у пациентов с сочетанием возрастной катаракты с клиническими проявлениями инволюционной соединительнотканной дисплазии

Purpose. Study of state of the Zonule of Zinn in patients with combination senile cataract with systemic involutional connective tissue dysplasia. Material and methods. 97 patients (97 eyes) – combination senile cataract with involutional pathology in connective tissue (the main group). 1st subgroup: 31 patients with kyphoscoliotic deformity of the 3d and 4th degree (classification by V.D. Chaklin (1973)); 2nd subgroup – 66 patients with chronic venous insufficiency 2nd and 3d degree (the CEAP classification) against the background of varicose veins of the lower extremity. Patients of both subgroups were comparable in terms of cataract stages and nuclear cataract lens density in Buratto classification. The control group – 55 patients (55 eyes) similar sex and age with senile cataracts without involutional connective tissue pathology. We estimated the symmetry of distance «lens equator – ciliary processes» in 2 meridians: at 6 and 12 hours. The presence of asymmetry of 0.3 mm or more was sign of weak zonular support (according to ultrasonic biomicroscopy). Results. In the control group, the distance was 0.3 mm in 3 eyes (5%), with intraoperative formation of folds in the anterior capsule. In 10 eyes of the 1st subgroup of the main group (32%), the presence of distance asymmetry was revealed: intraoperative, signs of subluxation of the lens of the 1st degree were detected in 7 eyes. In the 2nd subgroup of the main group, distance asymmetry was detected in 24 eyes (37%). Folded anterior lens capsule was determined intraoperative in 14 eyes (21%) during anterior capsulorhexis and lens mobility during nucleus emulsification. Conclusion. A statistically significant difference in frequency of asymmetries of distances «lens equator – ciliary processes» in 2 opposite meridians was revealed between groups of patients with senile cataract against the background of systemic somatic involutional pathology of connective tissue and without it (35% vs. 5%; p &lt; 0.01). Keywords: senile cataract, Zonule of Zinn, involutional changes in connective tissue, ultrasound biomicroscopy

Mean perfusion pressure in cardiopulmonary bypass as a factor of intraoperative acute kidney injury

The OBJECTIVE was to evaluate the role of mean perfusion pressure in the development of acute kidney injury (AKI) in patients operated with CPB.METHODS AND MATERIALS. A retrospective monocenter observational study was conducted among patients CPB (n=97) who underwent planned heart surgery using CPB. Inclusion criteria: age over 18 years, duration of surgery from 90 to 180 minutes, no signs of end-stage renal disease. The group was divided into subgroups according to the level of mean perfusion pressure (MPP): 1st – MPP&lt;60 mmHg, 2nd – MPP equal to and &gt;60 mmHg. Diagnosis of AKI was carried out on the basis of changes in serum creatinine and biomarkers (NGAL, IgG, albumin in urine). The studied parameters were recorded 15 minutes after the start and end of general anesthesia as well as 24 and 48 hours after surgery.RESULTS. In the 1st subgroup, the frequency of AKI was higher: after 24 hours – 48 (78.7 %), in the 2nd subgroup – 10 (27.8 %), and after 48 hours – 21 (34.4 %) and 5 (13.9 %), respectively. In the 1st subgroup, the need for renal replacement therapy was 5 (8.2 %), while in the 2nd subgroup only 1 patient needed renal replacement therapy (2.8 %). Also, in the 1st subgroup, a higher level of lactate was detected at the end of general anesthesia – the median in the 1st subgroup was 4.6 mmol/l (2.5–11.6), in the 2nd – 2.5 mmol/l (1.4–7.2) (p= 0.022). The levels of AKI biomarkers in urine after 24 hours also differed: NGAL in the 1st – 473.1 ng/ml (235.7–749.5) and in the 2nd –111.3 ng/ ml (53.4–152.9) (p=0.003), albumin 174.6 mg/l (151.2–236.9) and 35.8 mg/l (21.3–52.5) respectively (p=0.006), IgG – 61.7 mg/l (24.9–88.5) and 9.7 mg/l (7.1–14.4) (p=0.002).CONCLUSION. Mean perfusion pressure is an important indicator of the adequacy of cardiopulmonary bypass. Lowering it below 60 mmHg leads to hypoperfusion of the kidneys with the risk of acute kidney injury.

Role of DSM5 anxious distress specifier interview in acute manic episode: sociodemographic characteristics, clinical presentation and quality of life

BackgroundDSM 5 anxious distress specifier is one of the newly added specifiers for bipolar and related disorders. It may have impacts on the symptoms severity, insight, impulsivity, and different domains of quality of life of acute manic episodes of bipolar disorders. The current study aimed to study the effects of DSM 5 anxious distress specifier in acute manic episodes and its relation to sociodemographic data, clinical characteristics, and quality of life. 380 patients with the diagnosis of acute manic episode were recruited in the study, sociodemographic data, clinical features, DSM 5 anxious distress specifier interview, attitude and insight of the disorder, impulsivity and different aspects of quality of life were also evaluated in those patients.ResultsThe studied patients were divided into 2 subgroups according to the presence of high DSM5 anxious distress specifier interview score. The duration of a manic episode (P < 0.001), the severity of the manic episode (P < 0.001), and the presence of psychotic features (P = 0.002) were more common in the subgroup with high DSM 5 anxious distress. DSM 5 anxious distress specifier was severe (P < 0.001) and more frequent (P < 0.001) in the 1st subgroup than the 2nd one. There was a statistically significant difference regarding the attentional facet of the Barratt impulsiveness scale between the studied groups (P = 0.002). In addition, there was a statistically significant difference regarding the mean score (P < 0.001) and severe impairment (P < 0.001) domains of work and social adjustment scale between the 2 subgroups.ConclusionsDSM 5 anxious distress specifier interview is a very crucial parameter of evaluation the patients with acute manic episodes which may have implications on the clinical presentations, symptoms severity, impulsivity, and variable aspects of quality of life in those patients. All these implications might change the course, prognosis, and outcomes of an acute manic episode of bipolar disorder.

Prediction of bone metabolism disorders in premature babies

Introduction. Premature newborns suffer from osteopenia, which scientists attribute to vitamin D deficiency. Its deficiency leads to impaired development, the success of which depends on the first years of life. Given the increase in the number of premature babies born after in vitro fertilization, the question arises regarding the risk of them developing vitamin D deficiency.Aim to establish risk factors and develop prognostic tables for vitamin D deficiency in premature infants of the first three years of life born by in vitro fertilization and naturally.Materials and methods. We studied premature newborns (n = 189), which we divided into two groups, born by in vitro fertilization and naturally (comparison group). In each group, two subgroups of infants were identified. In the main in vitro fertilization group, the 1st subgroup included newborns weighing 1,000–1,500 g (n = 52), and the 2nd – weighing less than 1,000 g (n = 49). The comparison group included infants born naturally with a body weight of 1,000–1,500 g (n = 46) and those with a body weight of less than 1,000 g (n = 42).Results. Vitamin D deficiency was established in 67.7 ± 4.8% premature babies during the first year of life. In the second year of life, with intake of vitamin D 1000 IU/day, the level of calcidiol stabilized to normal value. The most sensitive group concerning vitamin D insufficiency is the group of babies with breast-milk substitutes. Factors associated with in vitro fertilization had not shown statistically significant influence on the vitamin D insufficiency in premature babies.Conclusion. We have proposed beneficial predictive tables for an individual risk evaluation of possible bone metabolic conditions in premature babies.

The role of clinical parameters and cathepsin S gene expression in predicting the development of postoperative pain in patients with hip osteoarthritis

Objective : to evaluate the significance of clinical indicators, expression of pain syndrome genes cathepsin S and pro-inflammatory cytokines in peripheral blood for predicting the development of postoperative pain (POP) in patients with hip osteoarthritis (HOA) before total arthroplasty (TA). Material and methods. The study included 31 patients with stages III–IV of HOA (mean age 61.3±9.8 years) who underwent TA and 26 healthy volunteers (control group). Depending on the presence or absence of POP, patients were divided into two subgroups: with POP (1st subgroup, n=12) and without POP (2nd subgroup, n=19). Patients were examined before and 6 months after surgery. Prior to TA, the level of pain was determined in all patients using the visual analogue scale (VAS), as well as using the DN4 and PainDETECT neuropathic pain questionnaires. Functional status was assessed by the WOMAC index. The development of POP ≥ 30 mm according to VAS was assessed 6 months after TA. Total RNA was isolated from whole blood and used to evaluate gene expression for cathepsin S, interleukin 1 (IL1 ), tumor necrosis factor α (TNF α ), and cyclooxygenase 2 (COX2) by quantitative real-time polymerase chain reaction. Results and discussion . Complaints of pain persisted in 12 (38.7%) patients 6 months after TA. Before surgery, the expression of cathepsin S, IL1 , TNF α , and COX2 genes was significantly higher in patients of both subgroups compared to healthy controls. In addition, in patients with POP who were not satisfied with the outcome of TA, the rates of neuropathic pain according to the DN4 questionnaire and cathepsin S gene expression were significantly higher than in other patients. At the same time, there was no significant difference in the expression of genes of pro-inflammatory cytokines in patients of the studied subgroups before TA. Conclusion . The development of POP in patients with HOA may be partially associated with its perception mechanisms disturbance, and an increase in the expression of the cathepsin S gene in the peripheral blood prior to TA can serve as its prognostic biomarker.

DIFFERENTIATED CHOICE OF POSTERIOR METHODS OF DISCONNECTION OF ANATOMICAL COMPONENTS OF THE ABDOMINAL WALL IN COMBINATION WITH ALLOPLASTY IN POSTOPERATIVE VENTRAL HERNIAS OF GIANT SIZE.

The aim: The aim of the article is to increase the effectiveness of the treatment of postoperative ventral hernias of giant size by a differentiated approach to the selection of the posterior technique of dissection of the anatomical components of the anterior abdominal wall in combination with alloplasty. Materials and methods: An analysis of the surgical treatment of 312 patients with giant postoperative ventral hernias (PVH). The main group consisted of 232 patients who underwent a differentiated approach to the selection of component separation in combination with alloplasty, taking into account intra-ab¬dominal pressure (IAP) when simulating hernioplasty during surgery. In the second control group (80 patients), surgical treatment of PVH of giant sizes was performed using only the posterior Carbonell technique. Results: In 78 patients of the 1st subgroup, IAP was 9.1±1.2 mm Hg. the posterior technique of separating anatomical components according to Carbonell was performed in combination with sublay alloplasty. In 80 patients of the II subgroup with IAP from 11.1 to 14.1±1.2 mm Hg - the TAR technique was performed with sublay alloplasty. In 74 patients of III subgroups with IAP from 16 to 20.1±1.2 mm Hg, performed the TAR technique, we improved in combination with IPOM alloplasty. Conclusions: An increase in the effectiveness of surgical treatment was achieved in patients of subgroup I, reducing the probability of intra-abdominal hypertension to 5.1% versus 11.2%, in patients of subgroup II to 5% versus 11.2%, and in patients of subgroup III to 1.4% versus 11.2% of the control group.